We are exploring a number of problems in the basic physiology of respiration and circulation in the hope of developing new concepts that will be useful in clinical medicine. The program consists of seven broad areas: (1) physiological effects of hypoxia: comparison of hypoxic hypoxia and carbon monoxide hypoxia; (2) studies on the relations between respiratory mechanics and the circulation; (3) pulmonary mechanics; (4) control of respiration; (5) gas transport in lung, placenta and solid tissue; (6) studies of specific circulations: pulmonary circulation, coronary circulation, cerebral circulation, and role of systemic vascular bed in control of venous return; (7) regulation of systemic, pulmonary and coronary circulation in awake and active dogs. The studies are carried out in isolated organs, anesthetized and unanesthetized animal preparations, and in human subjects, both normal and patients. In addition to conventional techniques in cardiovascular and respiratory physiology, behavioral techniques are used. Problems we are concerned with are: (1) Do the effects of hypoxia depend more on the level of the arterial or venous oxygen content or the level of the arterial or venous PO2? (2) Use of respiratory maneuvers and artificial ventilation to evaluate cardiovascular function and for treatment of pulmonary edema. (3) Development of new tests for the detection of early lung disease. (4) Role of peripheral chemoreceptors in respiratory and circulatory adjustments. (5) Are there special carriers for oxygen in tissues which facilitate oxygen transport? (6) How much can the cardiac output be changed by adjustments in the systemic circulation through changes in venous return? (7) How are the circulatory and respiratory adjustments to exercise and eating brought about?